Objective To establish an animal model by placing one end of PICC in the hepatic portal vein of a beagle dog and leaving the other end out of its body.Methods Six Beagle dogs were given respiration anesthesia through orotracheal intubation.An incision was made through the right rectus abdominalis to locate the superior mesenteric vein (SMA) and the main hepatic portal vein.The left branch of SMA was separated and cut to put PICC into the main hepatic portal vein before being ligated and fixed.The other end of PICC was elicited through the right abdominal wall and passed beneath the skin to the back neck and fastened in case of movement.Results The anesthetic effect was good and all the operations were successful.The mean operation time was about an hour and the mean blood loss was about 15 ml.The incision healed 5-7 d after operation.Conclusion The establishment of the model can improve the effects of liver-targeting drugs,which can cut down the dosage,lower the cost of treatment and experiment and reduce the adverse effect of medicines.Through PICC,we can directly draw blood from the hepatic portal vein to measure the blood concentration before the first pass elimination.Then according to the concentration,we can calculate the absorption rate in the gastrointestinal tract,which can facilitate related experimental studies.

Objective: To examine the dose-response association between cardiorespiratory fitness ( CRF ) and the risk of cardiovascular and cerebrovascular diseases. Methods: A joint search was performed in Chinese and English electronic databases, including China National Knowledge Infrastructure ( CNKI ) , Wanfang Data, VIP, CBM, PubMed, Embase and Web of Science, to retrieve publications reporting the correlation between CRF and the risk of cardiovascular and cerebrovascular diseases until May, 2021. The pooled risk was estimated using the random effects model, and the dose-response association was evaluated using restricted cubic splines. The source of heterogeneity was assessed by subgroup analysis, and the stability of the results was tested by the trim-and-fill method, while the publication bias was assessed using funnel plots. Results: Totally 37 280 literatures were identified, and 23 eligible studies were finally included in the analysis, which covered 2 605 622 subjects. There were 22 publications identified as high-quality. Meta-analysis revealed that the pooled risk of cardiovascular and cerebrovascular diseases reduced by 42% in the highest CRF group relative to the lowest CRF group ( OR=0.58, 95%CI: 0.52-0.65 ), and a one metabolic equivalent ( MET ) increase in CRF caused a 10% reduction in the pooled risk of cardiovascular and cerebrovascular diseases ( OR=0.90, 95%CI: 0.88-0.92 ). There was a negative linear correlation between CRF and the incidence of cardiovascular and cerebrovascular diseases ( P=0.396 ). Subgroup analysis identified gender, sample size and study regions as possible sources of heterogeneity, and sensitivity analysis showed that the study results were stable. Conclusions There is a negative linear correlation between CRF and the risk of cardiovascular and cerebrovascular diseases, and an increase in CRF may reduce the risk of cardiovascular and cerebrovascular diseases.

OBJECTIVETo investigate the chemical constituents of Peperomia tetraphylla.

METHODThe constituents of EtOAc-soluble portion were isolated and purified by chromatography. Their structures were identified by spectral features.

RESULTSix amides were isolated and identified as, aristololactam All (1), aristololactam B II (2), N-trans-feruloyltyramine (3), N-trans-sinapoyltyramine (4), N-trans-feruloylmethoxytyramine (5), N-p-coumaroyltyramine (6).

CONCLUSIONAll compounds were isolated from this plant for the first time.

AIM:To investigate the role of Rho-associated kinase ( ROCK) inhibitor fasudil in the formation of rabbit urethral stricture after injury and to observe the cell activity , migration and extracellular matrix synthesis in the rabbit urethra fibroblasts.METHODS:The rabbit model of urethral stricture was established by microsurgical techniques .The rabbits were divided into sham operation group , operation group and fasudil (3 mg/kg, 10 mg/kg, 30 mg/kg) groups.The diameter of the stenosis was measured by retrograde urethrography 3 months after surgery .The fibroblasts were isolated from urethral scar, and then incubated with fasudil (12.5 μmol/L, 25 μmol/L, 50 μmol/L) in the presence of transforming growth factor-β1 (TGF-β1, 10 μg/L).The untreated cells were used for control .The cell activity was measured by MTT assay.The cell migration ability was tested by the method of Transwell chambers .The protein expression of ROCK , α-smooth muscle actin (α-SMA) , collagen I and collagen III was determined by Western blot analysis .RESULTS:Fasudil significantly reduced formation of urethral stricture after injury (P<0.05).Cultured rabbit fibroblasts with different con-centrations of fasudil inhibited the cell activity and cell migration ability (P<0.05).The protein expression of ROCK,α-SMA, collagen I and collagen III was also inhibited by treatment with fasudil in a dose -dependent manner ( P<0.05 ) . CONCLUSION:Fasudil inhibits the formation of extracellular matrix and reduces the incidence of urethral stricture after injury by down-regulating TGF-β1-induced Rho/ROCK pathway activation in the rabbit urethra fibroblasts .

Objective Given that psychosocial stress can contribute to a series of diseases,such as inflammatory bowel disease and irritable bowel syndrome,we aimed to establish an experimental chronic restraint mouse intestinal stress injury model as a basis for exploring the pathogenic mechanism of chronic restraint stress-induced gastrointestinal diseases,and for developing preventive and curative measures.Methods Eighteen male SPF-grade BALB/c mice were acclimatized for 7 days and then divided into a control group and a chronic restraint stress group according to body weight,using a randomized numerical table method.The mice were subjected to restraint stress for 3 hours per day for 14 days to establish an intestinal injury model.The model was evaluated by observing body weight,pathological changes in intestinal histomorphology,expression of tight junction proteins,apoptosis of intestinal epithelial cells,and mRNA expression levels of inflammatory cytokines.Results After 14 days of chronic restraint stress,model mice showed weight loss,shortened duodenal villus height,abnormal crypt structure,a decreased villus/crypt ratio,colonic mucosal inflammatory cell infiltration,and irregular crypt structure.Protein immunoblotting,immunohistochemistry,and immunofluorescence staining showed that the expression levels of the duodenal and colonic tight junction proteins Occludin and Claudin-1 were significantly decreased in mice after chronic restraint stress(P＜0.05),while expression levels of the apoptotic protein cleaved-caspase-3 in intestinal epithelial cells were significantly increased(P＜0.05).Regarding the mRNA expression levels of intestinal inflammatory factors and chemokines,chronic restraint stress for 14 days significantly increased the gene expression levels of interleukin(IL)-1β,IL-6,monocyte chemoattractant protein-1(MCP-1),tumor necrosis factor-α,and IL-10 in the duodenum of mice(P＜0.05),and significantly increased the gene expression levels ofIL-1β,IL-6,and MCP-1 in the colon(P＜0.001).Conclusions The use of a behavioral restriction device to restrain mice continuously for 14 days led to abnormal intestinal tissue structure,intestinal barrier dysfunction,and intestinal epithelial cell apoptosis,and triggered an intestinal inflammatory response in the stressed mice,indicating successful establishment of a mouse model of intestinal injury by chronic restraint stress.

This article uses the analysis framework of the macro model of the health system to analyze the influenza vaccine policy documents issued by the state and governments at all levels from three perspectives: structure, process and results, and provides a scientific basis for improving the application strategy of influenza vaccine. It is suggested that on the basis of continuing to strengthen publicity, mobilization and organizational guarantee, measures to promote the application of influenza vaccine in China by exploring multi-channel financing mechanisms, combining the experience of new crown vaccination to improve the convenience of influenza vaccination, and scientifically setting vaccination rate targets, improve preparedness for an influenza pandemic.

This article uses the analysis framework of the macro model of the health system to analyze the influenza vaccine policy documents issued by the state and governments at all levels from three perspectives: structure, process and results, and provides a scientific basis for improving the application strategy of influenza vaccine. It is suggested that on the basis of continuing to strengthen publicity, mobilization and organizational guarantee, measures to promote the application of influenza vaccine in China by exploring multi-channel financing mechanisms, combining the experience of new crown vaccination to improve the convenience of influenza vaccination, and scientifically setting vaccination rate targets, improve preparedness for an influenza pandemic.

Diabetic macular edema is the major cause of vision impairment in patients with nonproliferative diabetic retinopathy.Thickness and pathological alterations in each retina layer of diabetic macular edema (DME) patients can be performed by optical coherence tomography (OCT) device.And retinal light sensitivity at specific retinal point and fixation state can be detected by microperimetry qualitatively and quantitatively.Moreover,OCT can discover pathological anatomical changes in the retina of DME patients,thus facilitating the interpretation of the structure-function relationship in DME with combination of microperimetry results.At present,there are various therapies for DME patients,and the primary method in evaluating therapeutic efficacy is to compare the pathological changes in the retina before and after treatment by OCT.Besides,microperimetry can provide information in visual function restoration.The combined application of OCT and microperimetry has broad prospects in the diagnosis and treatment of DME patients.

Objective By simulating acute hypoxic conditions, an experimental model of intestinal stress injury in plateau mice was established to explore the pathogenic mechanism of acute gastrointestinal diseases in plateau, and to lay foundation for preventive and therapeutic measures.MethodsThirty-six SPF-grade adult male BALB/c mice were randomly divided into four groups: normoxic 24 h, normoxic 72 h, hypoxic 24 h, and hypoxic 72 h, based on body weight using a randomized numerical table method, with nine mice in each group. Mice in the normoxic group were kept in a conventional barrier environment, while those in the hypoxic group were placed in a hypoxic chamber within the barrier environment with oxygen concentration set at 10% to simulate plateau conditions. They were subjected to stress for 24 h and 72 h, respectively, in order to establish a model of intestinal injury induced by acute hypoxia. After modeling, the mice were weighed, anesthetized with 1% pentobarbital sodium, and then euthanized by cervical dislocation. Duodenal and colonic tissues were collected. Histopathological morphology of intestinal tissues was observed after HE staining. Western blotting and immunohistochemistry were used to detect the expression levels of tight junction-related proteins in intestinal tissues. Real-time fluorescence quantitative PCR was performed to measure the expression levels of inflammatory cytokines and chemokines. TUNEL staining was used to assess apoptotic activity of intestinal epithelial cells, thus evaluating intestinal injury-related phenotypes in this model.Results Compared with the normoxic groups, mice in the 24 h and 72 h hypoxia groups showed weight loss, shortened duodenal villi, abnormal crypt structure, and decreased villus/crypt ratio. The colonic mucosa was infiltrated with inflammatory cells and irregular crypt structure. Expression levels of Occludin and zonula occludens-1 (ZO-1) were significantly decreased in duodenal and colonic tissues of mice in the 24 h and 72 h hypoxia groups (P<0.05). The expression of pro-apoptotic protein Bax was significantly up-regulated while expression of anti-apoptotic protein Bcl-2 was significantly down-regulated in duodenal tissues (P<0.05). Apoptotic activity of intestinal epithelial cells was significantly enhanced (P<0.05). In addition, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) mRNA levels were significantly increased in duodenal tissues after 24 and 72 h of hypoxic stress(P<0.05). After 24 h of hypoxic stress, there was no significant change in the expression levels of inflammatory cytokines in colon tissues (P>0.05), but after 72 h, the expression levels of pro-inflammatory factors IL-1β, TNF-α, IL-6, MCP-1, and anti-inflammatory factor IL-10 mRNAs significantly increased in colon tissues of mice (P<0.05).Conclusion The usage of a hypoxia chamber to simulate an acute hypoxic environment in plateau can lead to abnormal intestinal tissue structure, intestinal barrier dysfunction, and induce intestinal epithelial cell apoptosis, triggering an intestinal inflammatory response in stress mice. These findings indicate the successful construction of a mouse model for an acute hypoxic stress-induced intestinal injury.

Objective: To investigate the effect of the treatments for obstructive sleep apnea hypopnea syndrome (OSAHS) on the resistant hypertension (RH) of patients. Methods: Eighty patients with OSAHS and RH (blood pressure could not be controlled under 140/90 mmHg (1 mmHg=0.133 kPa) even with more than three kinds of antihypertensive drugs including diuretics) received surgery or continuous positive airway pressure (CPAP) treatment. The results of polysomnography monitoring, ambulatory blood pressure monitoring, and the dosage of antihypertensive medication were recorded before and six months after the treatment. Results: Apnea hypopnea index (AHI) decreased from (32.9±10.8) before treatment to (9.4±6.5) after treatment, while the lowest oxygen saturation (SaO₂) increased from (0.682±0.062) to (0.884±0.056), with significant differences (t value was 18.863 and 26.614, respectively; both P<0.001). Twenty-four hours systolic blood pressure (SBP)/diastolic blood pressure (DBP) decreased respectively from ((150.5±9.8)/(97.8±7.3)) mmHg to ((140.7±6.8)/(88.6±6.3)) mmHg, daytime SBP/DBP decreased from ((154.3±8.9)/(100.6±7.4)) mmHg to ((144.8±5.8)/(91.3±5.5)) mmHg, and nighttime SBP/DBP decreased from ((145.5±8.8)/(93.8±6.4)) mmHg to ((135.8±5.7)/(84.6±5.9)) mmHg, with significant differences (t value was 7.832, 6.903, 7.005, 6.848, 8.025, 7.554, respectively; all P<0.001). The reduction of nighttime SBP /DBP was ((11.5±2.2)/(10.2±3.1)) mmHg, and the reduction of daytime SBP/DBP was ((9.0±2.8)/(7.9±3.5)) mmHg. The reduction of nighttime SBP/DBP was more obvious than daytime SBP/DBP, with significant differences (t value was 9.732 and 6.936, respectively; both P<0.001). Before treatment, nighttime blood pressure decrease rate below 10% was showed in 75 percent of patients, and after treatment, this rate only in 37.5 percent of patients (χ²=22.857, P<0.01). The numbers of required antihypertensive drugs decreased in 45 (56.3%) cases, the average numbers of antihypertensive drugs decreased from (3.2±0.4) before treatment to (2.6±0.5) after treatment, with a significant difference (t=9.276, P<0.01). Conclusions After treatment of OSAHS, the blood pressure of the patients with OSAHS and RH dropped significantly, the circadian rhythm of blood pressure condition was better, the varieties of antihypertensive drugs taken in these patients were reduced significantly.